Mutations causing achondroplasia and thanatophoric dysplasia alter bFGF- induced calcium signals in human diploid fibroblasts

Mutations in the fibroblast growth factor receptor (FGFR) gene family recently have been shown to underlie several hereditary disorders of bone development, with specific FGFR3 mutations causing achondroplasia (Ach) and thanatophoric dysplasia (TD). However, for none of these mutations has the defect in receptor function been demonstrated directly and, therefore, for none has the pathophysiological mechanism of the disease been defined. Using our established techniques for single-cell ratiometric real-time calcium image analysis, we defined the nature of the basic fibroblast growth factor (bFGF)-induced calcium signal in human diploid fibroblasts, and, in blinded studies, have analyzed the bFGF-induced signals from 18 independent fibroblast cell lines, including multiple lines from patients with known mutant alleles of FGFR3 and syndromes of Ach or TD. Control cells responded with transient increases in intracellular calcium, with many cells showing oscillatory calcium waves. Homozygous Ach cell lines failed to signal, whereas heterozygous Ach lines responded nearly normally. We observed heterogeneous signals in TD heterozygotes: the unresponsive lines all turned out to carry TD1 alleles, whereas all responsive lines had TD2 alleles. Since FGFR1, 2 and 3 receptors are known to be expressed in fibroblasts, our results suggest that specific mutant FGFR3 alleles can function in a dosage-dependent dominant-negative fashion to inactivate FGFR signaling.      

Infection versus tumor in the spine: criteria for distinction with CT

To develop criteria to distinguish among pyogenic infection, nonpyogenic infection, and neoplastic processes in the spine by means of computed tomography (CT), the authors retrospectively analyzed 17 cases of pyogenic infection (20 sites), 40 cases of neoplastic disease (56 sites), and five cases of granulomatous infection (eight sites). Reliable criteria for pyogenic infection were complete prevertebral soft-tissue involvement, diffuse osteolytic destruction, gas within both bone and soft tissue, and a process centering on an intervertebral disk. Neoplastic disease was characterized by posterior element involvement, partial or absent prevertebral soft-tissue swelling, and osteoblastic alterations. In a limited number of cases, nonpyogenic infection was characterized by focal lytic bone involvement and marginal sclerosis. Blinded testing of these criteria indicated potential for improved diagnostic accuracy in clinical practice.     

Malignant melanoma of the eye: treatment of posterior uveal lesions by Co-60 plaque radiotherapy versus enucleation

Survival rates and visual acuity of 100 patients treated for posterior uveal malignant melanoma by cobalt-60 plaque radiotherapy were compared with 150 patients treated by enucleation for the same disease. Life-table comparisons of the entire group showed significant differences in survival rates, with plaque radiotherapy patients appearing to fare better. However, when patients with small or medium tumors were compared, only slight differences were seen, implying that criteria used to select patients for treatment may affect interpretation. The two groups were also compared using the Cox proportional hazards model, which predicts survival based on the impact of clinical variables. In this analysis, the survival rates of the plaque radiotherapy group were no worse than those of the enucleation group. The advantage of conservative therapy lies in the potential to preserve useful vision over a considerable time. Because patients were specifically selected for treatment modality and because the study size used to calibrate the Cox model was small, the results of this study must be interpreted with caution.     

Arthritis: roles of radiography and other imaging techniques in evaluation

Imaging studies are performed on patients with arthritis for a variety of reasons: to determine whether an arthritic condition is present; to establish the specific diagnosis; to determine the extent of disease; to assess the activity of disease; to detect complications of disease; to evaluate progression of disease; to judge the efficacy of drug treatment; to help in selection of surgical candidates; to aid in the choice of surgical procedures; to size, design, or fabricate prostheses; and to identify complications of surgery. Conventional radiography is still the mainstay of all examinations in arthritic patients. Arthrography is best applied to evaluate complications of disease and of surgery, although it may be useful in disease detection and in determining the specific diagnosis. Nuclear medicine studies are best used to identify complications of surgery and may also be useful to assess disease activity or extent. Ultrasound is useful to detect dissecting synovial cysts and deep venous thrombosis. The most valuable role of computed tomography is in the design and fabrication of prostheses and in evaluating complex anatomy of involved joints. Magnetic resonance imaging may be useful in early detection of articular cartilage damage and may assist in determination of the specific diagnosis; enhancement with contrast material may aid in assessment of disease activity.     

A comparison of a Patient Enablement Instrument (PEI) against two established satisfaction scales as an outcome measure of primary care consultations

OBJECTIVES: We aimed to compare a new primary care outcome measure-the Patient Enablement Instrument (PEI)-against two established satisfaction measures [the Medical Interview Satisfaction Scale (MISS) and the Consultation Satisfaction Questionnaire (CSQ)]. Specifically, we sought (i) to test whether enablement and satisfaction are related or separate concepts; and (ii) to assess whether the internal consistency of the PEI might be enhanced by the inclusion of items from the satisfaction instruments. METHODS: Questionnaire forms containing the three instruments in a variety of combinations were distributed to a total of 818 patients attending for routine surgery consultations in three urban general practices of varying socio-economic mix. The main outcome measures were: scores on the PEI; scores on the CSQ, the MISS and their individual components; rank correlations between scores on the PEI and scores on the CSQ, the MISS and their component subscales; and Cronbach's alpha coefficient for the PEI. RESULTS: Overall mean scores, expressed as percentages of maximum scores attainable, were 44.1% for the PEI, 76.9% for the CSQ and 77.6% for the MISS. Rank correlations between PEI scores and scores for the complete CSQ and MISS instruments were 0.48 (P < 0.01) and 0.47 (P < 0.01), respectively. Correlations of PEI scores with individual component scores on the CSQ were generally lower and ranged from 0.14 to 0.53; correlations of PEI scored with MISS component scores were also generally lower and ranged from 0.21 to 0.53. Internal consistency of the PEI items (assessed by Cronbach's alpha coefficient) was lowered when items from the CSQ or MISS were added. CONCLUSIONS: The study shows that 'enablement' is a primary care outcome measure which is related to but is different from general satisfaction.